On November 9, 2020 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported the presentation of new preclinical data supporting its lead clinical oncology program, RTX-240, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Rubius Therapeutics, NOV 9, 2020, View Source [SID1234570309]). The meeting is being held virtually from November 9-14, 2020.

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RTX-240 is an allogeneic, off-the-shelf Red Cell Therapeutic that is engineered to mimic the human immune system by stimulating adaptive and innate immunity to generate an anti-tumor immune response. Rubius Therapeutics is currently enrolling patients in the Phase 1/2 clinical trial of RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors. In addition, RTX-240 is being evaluated in a second Phase 1 arm of the clinical trial for the treatment of patients with relapsed/refractory acute myeloid leukemia.

"The preclinical data presented at SITC (Free SITC Whitepaper) indicate that RTX-240 has the ability to potently activate and expand CD8 T cells and natural killer (NK) cells in vitro and in vivo," said Laurence Turka, M.D., chief scientific officer of Rubius Therapeutics. "In addition, the preclinical data demonstrated that RTX-240 promotes NK cell killing of a myeloid leukemia cell line, giving us confidence that these promising preclinical results may translate into clinical benefit for patients with relapsed/refractory acute myeloid leukemia, where the activation status of the NK cells is linked to clinical outcomes. Finally, our surrogate model of RTX-240 demonstrated significant expansion of CD8 T cells and NK cells in a colorectal cancer model and potent anti-tumor activity in a melanoma model – giving us added conviction that RTX-240 may be an effective treatment for relapsed/refractory or locally advanced solid tumors."

Data Summary

RTX-240, an Allogeneic Engineered Red Blood Cell Expressing 4-1BBL and IL-15TP, Promotes NK Cell Functionality In Vitro and In Vivo

RTX-240 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BBL and IL-15TP (trans-presentation of IL-15 on IL-15Rα) on the cell surface in their native forms. RTX-240 is designed to stimulate innate and adaptive immunity by activating NK cells and T cells inside the patient’s body to generate an anti-tumor immune response. RTX-240 preclinical data demonstrated:
° RTX-240 led to increased CD8 T cell and NK cell expansion and activation in vitro compared to the combination of a 4-1BB agonist antibody plus recombinant IL-15 which was directly correlated with the percentage of 4-1BBL and IL-15TP expressed on the cell surface
° RTX-240 expanded CD56dim NK cells, a cell population with high cytotoxicity
° RTX-240 promoted NK cell-killing of a myeloid leukemia cell line, K562, and this was accompanied by increased NK cell degranulation and activation
° A murine surrogate for RTX-240, mRBC-240, promoted significant expansion of CD8 T cells and NK cells in vivo in a murine model of colorectal cancer (CT26)
° mRBC-240 demonstrated potent antitumor activity in a B16F10 melanoma model that was directly correlated with the expansion of terminally differentiated NK cells in the tumors
About the RTX-240 Clinical Trial
Rubius Therapeutics is enrolling patients in a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study of RTX-240. The study contains two Phase 1 dose escalation arms: one in patients with relapsed/refractory or locally advanced solid tumors and another in patients with relapsed/refractory acute myeloid leukemia. These two Phase 1 arms will determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-240 in patients with solid tumors as well as in patients with relapsed/refractory AML. The trial will also assess the pharmacodynamics of RTX-240 measured by changes in T and NK cell number and function relative to baseline and anti-tumor activity in both patient populations. The study will include an expansion phase in specified tumor types during the Phase 2 portion of the solid tumor arm. The extent to which the COVID-19 pandemic may impact Rubius’ ability to enroll patients in the trial will depend on future developments.

About RTX-240
RTX-240 is an allogeneic cellular therapy product candidate that is being evaluated for the treatment of patients with relapsed/refractory or locally advanced solid tumors or relapsed/refractory acute myeloid leukemia. RTX-240 is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BBL and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms and is designed to stimulate innate and adaptive immunity by activating NK cells and T cells inside the patient’s body to generate an anti-tumor immune response.